Core B supports every project within the Program by providing access to state-of-the-art RNAi tools. Short hairpin RNAs (shRNAs) were developed with the support of this program, and ongoing innovations by Core B and Program investigators have helped to make these extremely powerful biological tools. During the past funding period, the Core devised methods to rapidly engineer mice carrying regulated shRNA expression cassettes, devised strategies for functionally validating shRNAs in a multiplexed fashion, and created a third generation of RNAi libraries corresponding to annotated protein coding genes in humans and mice. During the upcoming period of requested support, the core proposes to aid Program investigators through five general aims. First, the program will continue to provide access to state-of-the-art RNAi tools for analyzing either single gene knockdowns or for performing pooled RNAi screens. Second, the Core will work with investigators to operate the sensor assay to identify optimal shRNAs tools against genes of interest. Third, the core will produce custom RNAi libraries against sets of genes that are of interest to Program investigators. Fourth, the Core will produce mice carrying regulated RNAi cassettes and aid investigators in combining these with other desired genetic lesions. Finally, the Core will carry on its efforts to improve RNAi technologies and make those innovations available to the Program and to the community at large.